Acta Pædiatrica ISSN 0803-5253
REGULAR ARTICLE
Amplitude-integrated electroencephalography shows that doxapram influences the brain activity of preterm infants Christine Czaba-Hnizdo ([email protected]), Monika Olischar, Zsofia Rona, Manfred Weninger, Angelika Berger, Katrin Klebermass-Schrehof Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
Keywords Amplitude-integrated electroencephalography, Brain activity, Doxapram, Preterm infant, Seizure activity Correspondence Christine Czaba-Hnizdo, MD, Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Tel: +43-1-40400-3232 | Fax: +43-1-40400-3165 | Email: [email protected] Received 18 December 2013; revised 3 April 2014; accepted 6 May 2014. DOI:10.1111/apa.12681
ABSTRACT Aim: The aim of this study was to measure the brain activity of preterm infants treated with caffeine citrate and doxapram for preterm apnoea, using amplitude-integrated electroencephalography (aEEG), to identify any adverse effects on cerebral function. Methods: We analysed the aEEG tracings of 13 preterm infants grade II (27) or central nervous system malformation or infection, were excluded. Results were compared with a consecutive control group of infants of the same gestational age and with aEEG measurements at comparable time points who did not receive doxapram. The following were recorded for each patient: sex, gestational age at birth, birthweight, antenatal steroids, multiple birth, intraventricular haemorrhage grade I or II (26), periventricular leucomalacia grade I or II (27), respiratory distress syndrome, chronic lung disease, persistent ductus arteriosus, necrotising enterocolitis, retinopathia praematurorum, days of ventilation, clinical seizure activity and death. Gestational age was determined from the date of the mother’s last menstrual period and according to antenatal ultrasound scans. The study was approved by the local ethics committee. Amplitude-integrated EEG Amplitude-integrated electroencephalography was recorded as a single channel EEG from biparietal surface disc electrodes using a CFM (CFM 5330; Lectromed Devices Ltd., Letchworth, UK, and Olympic CFM 6000; Natus Medical Incorporated, San Carlos, CA, USA). The detailed aEEG technique has been described elsewhere (21). The quality of the recordings was monitored by continuous impedance tracing, and the duration of the
recordings was at least 90 min. Handling or routine nursing care periods were marked on the tracing. Evaluation of aEEG tracings Amplitude-integrated electroencephalography tracings were analysed with regard to background activity (percentages of continuous and discontinuous patterns), occurrence of sleep-wake cycling and appearance of electrographic seizure activity. Tracings were evaluated visually and € m-Westas et al. (22). classified according to Hellstro Descriptive analysis of the aEEG tracings was carried out by dividing each trace in 10-min epochs. These 10-min epochs were classified into the five different background patterns: flat trace, continuous low voltage pattern, burst suppression pattern, discontinuous pattern and continuous pattern. Additionally, bursts per hour, defined as amplitudes >100 lV, were calculated. Sleep-wake cycling was defined as cyclic variations of aEEG background activity, and electrographic seizure activity was defined as either single seizures, repetitive seizures or saw tooth pattern. Both the definitions were € m-Westas et al. (22). according to Hellstro Cranial ultrasound Cranial ultrasound scans were performed twice in the first week of life and then once a week until discharge. Intraventricular haemorrhage and periventricular leukomalacia were classified according to Volpe (23) and de Vries et al. (24), respectively. Medication According to the guidelines in our department, every preterm infant with a gestational age of ≤32 weeks received caffeine citrate as standard treatment from first day of life. The loading dosage was 20 mg/kg/days, and the maintenance dosage was 10 mg/kg/days once a day until at least a corrected age of 34 weeks of gestation. Additional doxapram treatment was started if there were more than six episodes of desaturation below 70% peripheral saturation per hour and, or, bradycardia below 80 bpm per hour and, or, more than two episodes of assisted ventilations by ambu bag were necessary. A single loading dosage of 0.5–1.5 mg/kg doxapram was applied, followed by a continuous infusion of 0.5–1 mg/kg/ h. Tracings were performed during the course of the maintaining dose. Statistical analysis The frequency of the occurrence of each aEEG pattern, as a percentage, was determined as the ratio between the duration of the pattern and the duration of the entire recording. Frequencies of the patterns are given as median and range. Occurrences of sleep-wake cycling as well as electrographic seizure activity are given in percentages for each group, calculated by dividing the number of patients
©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. 922–927
923
Doxapram influences brain activity of preterm infants
Czaba-Hnizdo et al.
with sleep-wake cycling or electrographic seizure activity by the total number of patients in each group. Statistical analysis was performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA). P-values were calculated two-sided, and p < 0.05 was considered significant.
RESULTS During the study period, 948 preterm infants of
REGULAR ARTICLE
Amplitude-integrated electroencephalography shows that doxapram influences the brain activity of preterm infants Christine Czaba-Hnizdo ([email protected]), Monika Olischar, Zsofia Rona, Manfred Weninger, Angelika Berger, Katrin Klebermass-Schrehof Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
Keywords Amplitude-integrated electroencephalography, Brain activity, Doxapram, Preterm infant, Seizure activity Correspondence Christine Czaba-Hnizdo, MD, Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Tel: +43-1-40400-3232 | Fax: +43-1-40400-3165 | Email: [email protected] Received 18 December 2013; revised 3 April 2014; accepted 6 May 2014. DOI:10.1111/apa.12681
ABSTRACT Aim: The aim of this study was to measure the brain activity of preterm infants treated with caffeine citrate and doxapram for preterm apnoea, using amplitude-integrated electroencephalography (aEEG), to identify any adverse effects on cerebral function. Methods: We analysed the aEEG tracings of 13 preterm infants grade II (27) or central nervous system malformation or infection, were excluded. Results were compared with a consecutive control group of infants of the same gestational age and with aEEG measurements at comparable time points who did not receive doxapram. The following were recorded for each patient: sex, gestational age at birth, birthweight, antenatal steroids, multiple birth, intraventricular haemorrhage grade I or II (26), periventricular leucomalacia grade I or II (27), respiratory distress syndrome, chronic lung disease, persistent ductus arteriosus, necrotising enterocolitis, retinopathia praematurorum, days of ventilation, clinical seizure activity and death. Gestational age was determined from the date of the mother’s last menstrual period and according to antenatal ultrasound scans. The study was approved by the local ethics committee. Amplitude-integrated EEG Amplitude-integrated electroencephalography was recorded as a single channel EEG from biparietal surface disc electrodes using a CFM (CFM 5330; Lectromed Devices Ltd., Letchworth, UK, and Olympic CFM 6000; Natus Medical Incorporated, San Carlos, CA, USA). The detailed aEEG technique has been described elsewhere (21). The quality of the recordings was monitored by continuous impedance tracing, and the duration of the
recordings was at least 90 min. Handling or routine nursing care periods were marked on the tracing. Evaluation of aEEG tracings Amplitude-integrated electroencephalography tracings were analysed with regard to background activity (percentages of continuous and discontinuous patterns), occurrence of sleep-wake cycling and appearance of electrographic seizure activity. Tracings were evaluated visually and € m-Westas et al. (22). classified according to Hellstro Descriptive analysis of the aEEG tracings was carried out by dividing each trace in 10-min epochs. These 10-min epochs were classified into the five different background patterns: flat trace, continuous low voltage pattern, burst suppression pattern, discontinuous pattern and continuous pattern. Additionally, bursts per hour, defined as amplitudes >100 lV, were calculated. Sleep-wake cycling was defined as cyclic variations of aEEG background activity, and electrographic seizure activity was defined as either single seizures, repetitive seizures or saw tooth pattern. Both the definitions were € m-Westas et al. (22). according to Hellstro Cranial ultrasound Cranial ultrasound scans were performed twice in the first week of life and then once a week until discharge. Intraventricular haemorrhage and periventricular leukomalacia were classified according to Volpe (23) and de Vries et al. (24), respectively. Medication According to the guidelines in our department, every preterm infant with a gestational age of ≤32 weeks received caffeine citrate as standard treatment from first day of life. The loading dosage was 20 mg/kg/days, and the maintenance dosage was 10 mg/kg/days once a day until at least a corrected age of 34 weeks of gestation. Additional doxapram treatment was started if there were more than six episodes of desaturation below 70% peripheral saturation per hour and, or, bradycardia below 80 bpm per hour and, or, more than two episodes of assisted ventilations by ambu bag were necessary. A single loading dosage of 0.5–1.5 mg/kg doxapram was applied, followed by a continuous infusion of 0.5–1 mg/kg/ h. Tracings were performed during the course of the maintaining dose. Statistical analysis The frequency of the occurrence of each aEEG pattern, as a percentage, was determined as the ratio between the duration of the pattern and the duration of the entire recording. Frequencies of the patterns are given as median and range. Occurrences of sleep-wake cycling as well as electrographic seizure activity are given in percentages for each group, calculated by dividing the number of patients
©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. 922–927
923
Doxapram influences brain activity of preterm infants
Czaba-Hnizdo et al.
with sleep-wake cycling or electrographic seizure activity by the total number of patients in each group. Statistical analysis was performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA). P-values were calculated two-sided, and p < 0.05 was considered significant.
RESULTS During the study period, 948 preterm infants of
